Human infection with Pseudomonas aeruginosa is an increasingly serious problem. Current infection and mortality rates with Pseudomonas infections are high despite the major new antibiotics. A previously unrecognized phenomenon that appears to contribute to the high mortality rate in Pseudomonas infections is the antagonism by calcium of antibiotics. Physiologic concentrations of calcium have been shown to antagonize the activities of polymyxin, colistin, gentamicin, and tobramycin on P. aeruginosa in vitro. The degree of antagonism by calcium of antibiotic varies with the strain of Pseudomonas. Calcium has little antagonistic effect on antibiotics with some strains of Pseudomonas. Calcium has little antagonistic effect on antibiotics with some strains of Pseudomonas; it completely prevents the activity of antibiotics on other strains. The relative antagonism of calcium in vitro to antibiotics appears to correlate with the efficacy of these antibiotics in vivo in treating experimental infection of mice. The proposed study is designed to answer three major questions: (1) What is the significance in vivo of the antagonism by calcium to antibiotics used in Pseudomona infections? Two types of studies will be done. (2) Is it possible to detect the antagonism by calcium with simple laboratory tests? (3) How may the antagonistic effect of calcium in vivo be circumvented in the therapy of infections? Studies are planned on the pathogenesis of experimental Pseudomonas infections, on the role of combined therapy with two antibiotics, and on the value of antiserum and immunization in the treatment of resistant Pseudomona infections.